Patients with acute and chronic coronary syndromes have elevated long-term thrombin generation.

Coronary artery disease is a leading cause of morbidity and mortality worldwide. Despite significant advances in revascularization strategies and antiplatelet therapy with aspirin and/or P2Y12 receptor antagonist, patients with acute coronary syndrome (ACS) continue to be at long-term risk of further cardiovascular events. Besides platelet activation, the role of thrombin generation (TG) in atherothrombotic complications is widely recognized. In this study, we hypothesized that there is an elevation of coagulation activation persists beyond 12 months in patients with ACS and chronic coronary syndrome (CCS) when compared with healthy controls. We measured TG profiles of patients within 72 h after percutaneous coronary intervention, at 6-month, 12-month and 24-month. Our results demonstrated that TG of patients with ACS (n = 114) and CCS (n = 40) were persistently elevated when compared to healthy individuals (n = 50) in peak thrombin (ACS 273.1 nM vs CCS 287.3 nM vs healthy 234.3 nM) and velocity index (ACS 110.2 nM/min vs CCS 111.0 nM/min vs healthy 72.9 nM/min) at 24-month of follow-up. Our results suggest a rationale for addition of anticoagulation to antiplatelet therapy in preventing long-term ischemic events after ACS. Further research could clarify whether the use of TG parameters to enable risk stratification of patients at heightened long-term procoagulant risk who may benefit most from dual pathway inhibition.

Long-term prediction of algal chlorophyll based on empirical models and the machine learning approach in relation to trophic variation in Juam Reservoir, Korea.

This study analyzed spatiotemporal variation and long-term trends in water quality indicators and trophic state conditions in an Asian temperate reservoir, Juam Reservoir (JR), and developed models that forecast algal chlorophyll (CHL-a) over a period of 30 years, 1993-2022. The analysis revealed that there were longitudinal gradients in water quality indicators along the reservoir, with notable influences from tributaries and seasonal variations in nutrient regimes and suspended solids. The empirical model showed phosphorus was found to be the key determinant of algal biomass, while suspended solids played a significant role in regulating water transparency. The trophic state indices indicated varying levels of trophic status, ranging from mesotrophic to eutrophic. Eutrophic states were particularly observed in zones after the summer monsoons, indicating a heightened risk of algal blooms, which were more prevalent in flood years. The analysis of trophic state index deviation suggested that phosphorus availability strongly influences the reservoir trophic status, with several episodes of non-algal turbidity at each site during Mon. Increases in non-algal turbidity were more prevalent during the monsoon in flood years. This study also highlighted overall long-term trends in certain water quality parameters, albeit with indications of shifting pollution sources towards non-biodegradable organic matter. According to the machine learning tests, a random forest (RF) model strongly predicted CHL-a (R2 = 0.72, p < 0.01), except for algal biomass peaks (>60 µg/L), compared to all other models. Overall, our research suggests that CHL-a and trophic variation are primarily regulated by the monsoon intensity and predicted well by the machine learning RF model.

Simultaneous cardiocerebral infarctions: a five-year retrospective case series reviewing natural history.

Introduction: Concurrent cardiocerebral infarction (CCI), a rare condition defined as simultaneous occlusions in the cerebrovascular and coronary vessels, has high mortality but very limited literature on optimum treatment methods. A better understanding of the natural history and effect of treatment would improve patient outcomes. Methods: Using our prospective stroke database from 2014 to 2018, ten consecutive patients with CCI were identified (incidence = 0.29%). We recorded patient demographics, cardiovascular risk factors, cardiac and cerebral occlusions, circumstances of admission and management of each patient. Patient notes and imaging findings were reviewed to determine the underlying cause of CCI. Results: Median National Institute of Health Stroke Scale score was 15 (range 4-27). Mean patient age was 59 years and 90% were men. Two patients were treated with intravenous tissue plasminogen activator (IV tPA) only and three underwent endovascular treatment in both the cerebral and coronary vessels sequentially. One patient underwent percutaneous coronary intervention (PCI) only and two underwent PCI after IV tPA therapy. Two patients were conservatively treated due to poor premorbid status. At the three-month follow-up, five patients had excellent functional outcomes (modified Rankin Scale 0-1) while three died. Conclusion: CCI is a rare but devastating clinical scenario, with high incidence of morbidity and mortality. Treatment strategy can impact patient outcome, and further research is warranted on the ideal acute and post-reperfusion treatments for CCI. In this series, IV tPA at stroke doses appeared to be the preferred initial step for its treatment, with subsequent coronary or cerebral endovascular therapy, if necessary.

Asia Pacific TAVI registry (an APSIC initiative): initial report of early outcomes: Asia Pacific TAVI registry.

AIMS: The aim of the study was to report the clinical experience, 30-day mortality and acute outcomes of patients undergoing transcatheter aortic valve implantation (TAVI) in the Asia Pacific region. METHODS AND RESULTS: The Asia Pacific TAVI registry is an international, multicentre, prospective, observational registry managed under the auspices of the Asian Pacific Society of Interventional Cardiology (APSIC). Patients undergoing TAVI in seven centres from Hong Kong, Japan, Philippines, Singapore and Taiwan, treated with TAVI devices for severe symptomatic aortic stenosis, were assessed. This first review presents the acute results and 30-day mortality. A multivariable analysis was also performed to identify independent predictors of early all-cause mortality. The enrolment was from 2009 to 2017 and a total of 1,125 patients were recruited. The 30-day mortality rate was 2.5%. Baseline logistic EuroSCORE more than 16 was independently associated with a 2.8-times increased risk of 30-day all-cause mortality (p=0.016). Post-procedural stroke (HR 4.9, p=0.008) was also associated with increased mortality. CONCLUSIONS: This initial report of the Asia Pacific TAVI registry demonstrated good acute success and low 30-day mortality. The preprocedural logistic EuroSCORE and post-procedural stroke incidence were strongly associated with acute mortality. Further attempts to reduce post-procedural stroke should be explored.

Disrupting the LINC complex by AAV mediated gene transduction prevents progression of Lamin induced cardiomyopathy.

Mutations in the LaminA gene are a common cause of monogenic dilated cardiomyopathy. Here we show that mice with a cardiomyocyte-specific Lmna deletion develop cardiac failure and die within 3-4 weeks after inducing the mutation. When the same Lmna mutations are induced in mice genetically deficient in the LINC complex protein SUN1, life is extended to more than one year. Disruption of SUN1's function is also accomplished by transducing and expressing a dominant-negative SUN1 miniprotein in Lmna deficient cardiomyocytes, using the cardiotrophic Adeno Associated Viral Vector 9. The SUN1 miniprotein disrupts binding between the endogenous LINC complex SUN and KASH domains, displacing the cardiomyocyte KASH complexes from the nuclear periphery, resulting in at least a fivefold extension in lifespan. Cardiomyocyte-specific expression of the SUN1 miniprotein prevents cardiomyopathy progression, potentially avoiding the necessity of developing a specific therapeutic tailored to treating each different LMNA cardiomyopathy-inducing mutation of which there are more than 450.